6Z06

Crystal structure of Puumala virus Gc in complex with Fab 4G2

Summary for 6Z06

• Entry DOI: 10.2210/pdb6z06/pdb
• Descriptor: Fab 4G2 Heavy chain, Fab 4G2 Light chain, Envelope polyprotein, ... (5 entities in total)
• Functional Keywords: viral glycoprotein, class ii fusion glycoprotein, neutralizing antibody complex, hantavirus glycoprotein gc, bank vole antibody, viral protein
• Biological source: Myodes glareolus; More
• Total number of polymer chains: 3
• Total formula weight: 99225.02

Authors

Rissanen, I.R.,Stass, R.,Krumm, S.A.,Seow, J.,Hulswit, R.J.G.,Paesen, G.C.,Hepojoki, J.,Vapalahti, O.,Lundkvist, A.,Reynard, O.,Volchkov, V.,Doores, K.J.,Huiskonen, J.T.,Bowden, T.A. (deposition date: 2020-05-07, release date: 2020-12-30, Last modification date: 2024-01-24)

Primary citation

Rissanen, I.,Stass, R.,Krumm, S.A.,Seow, J.,Hulswit, R.J.,Paesen, G.C.,Hepojoki, J.,Vapalahti, O.,Lundkvist, A.,Reynard, O.,Volchkov, V.,Doores, K.J.,Huiskonen, J.T.,Bowden, T.A.
Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein.
Elife, 9:-, 2020

PubMed Abstract: The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryo-electron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc) lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.

PubMed: 33349334
DOI: 10.7554/eLife.58242

Experimental method

X-RAY DIFFRACTION (3.5 Å)